X-ray radiation-induced and targeted photodynamic therapy with folic acid-conjugated biodegradable nanoconstructs

Sandhya Clement,1,2,* Wenjie Chen,1,* Wei Deng,1,2 Ewa M Goldys1,2 1Australian Research Council Centre of Excellence for Nanoscale BioPhotonics (CNBP), Department of Physics and Astronomy, Macquarie University, Sydney, NSW, Australia; 2The Graduate School of Biomedical Engineering, University of Ne...

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Autores principales:	Clement S, Chen W, Deng W, Goldys EM
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	PLGA nanoparticles Verteporfin Singlet oxygen generation Photodynamic therapy X-ray PDT folic acid targeting Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/7e8c001399a14713b41bd5ca99ed6a62
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spelling	oai:doaj.org-article:7e8c001399a14713b41bd5ca99ed6a622021-12-02T01:28:38ZX-ray radiation-induced and targeted photodynamic therapy with folic acid-conjugated biodegradable nanoconstructs1178-2013https://doaj.org/article/7e8c001399a14713b41bd5ca99ed6a622018-06-01T00:00:00Zhttps://www.dovepress.com/x-ray-radiation-induced-and-targeted-photodynamic-therapy-with-folic-a-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Sandhya Clement,1,2,* Wenjie Chen,1,* Wei Deng,1,2 Ewa M Goldys1,2 1Australian Research Council Centre of Excellence for Nanoscale BioPhotonics (CNBP), Department of Physics and Astronomy, Macquarie University, Sydney, NSW, Australia; 2The Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW, Australia *These authors contributed equally to this work Introduction: The depth limitation of conventional photodynamic therapy (PDT) with visible electromagnetic radiation represents a challenge for the treatment of deep-seated tumors. Materials and methods: To overcome this issue, we developed an X-ray-induced PDT system where poly(lactide-co-glycolide) (PLGA) polymeric nanoparticles (NPs) incorporating a photosensitizer (PS), verteporfin (VP), were triggered by 6 MeV X-ray radiation to generate cytotoxic singlet oxygen. The X-ray radiation used in this study allows this system to breakthrough the PDT depth barrier due to excellent penetration of 6 MeV X-ray radiation through biological tissue. In addition, the conjugation of our NPs with folic acid moieties enables specific targeting of HCT116 cancer cells that overexpress the folate receptors. We carried out physiochemical characterization of PLGA NPs, such as size distribution, zeta potential, morphology and in vitro release of VP. Cellular uptake activity and cell-killing effect of these NPs were also evaluated. Results and discussion: Our results indicate that our nanoconstructs triggered by 6 MeV X-ray radiation yield enhanced PDT efficacy compared with the radiation alone. We attributed the X-ray-induced singlet oxygen generation from the PS, VP, to photoexcitation by Cherenkov radiation and/or reactive oxygen species generation facilitated by energetic secondary electrons produced in the tissue. Conclusion: The cytotoxic effect caused by VP offers the possibility of enhancing the radiation therapy commonly prescribed for the treatment of cancer by simultaneous PDT. Keywords: PLGA nanoparticles, verteporfin, singlet oxygen generation, photodynamic therapy, X-ray PDT, folic acid targetingClement SChen WDeng WGoldys EMDove Medical PressarticlePLGA nanoparticlesVerteporfinSinglet oxygen generationPhotodynamic therapyX-ray PDTfolic acid targetingMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 3553-3570 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	PLGA nanoparticles Verteporfin Singlet oxygen generation Photodynamic therapy X-ray PDT folic acid targeting Medicine (General) R5-920
spellingShingle	PLGA nanoparticles Verteporfin Singlet oxygen generation Photodynamic therapy X-ray PDT folic acid targeting Medicine (General) R5-920 Clement S Chen W Deng W Goldys EM X-ray radiation-induced and targeted photodynamic therapy with folic acid-conjugated biodegradable nanoconstructs
description	Sandhya Clement,1,2,* Wenjie Chen,1,* Wei Deng,1,2 Ewa M Goldys1,2 1Australian Research Council Centre of Excellence for Nanoscale BioPhotonics (CNBP), Department of Physics and Astronomy, Macquarie University, Sydney, NSW, Australia; 2The Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW, Australia *These authors contributed equally to this work Introduction: The depth limitation of conventional photodynamic therapy (PDT) with visible electromagnetic radiation represents a challenge for the treatment of deep-seated tumors. Materials and methods: To overcome this issue, we developed an X-ray-induced PDT system where poly(lactide-co-glycolide) (PLGA) polymeric nanoparticles (NPs) incorporating a photosensitizer (PS), verteporfin (VP), were triggered by 6 MeV X-ray radiation to generate cytotoxic singlet oxygen. The X-ray radiation used in this study allows this system to breakthrough the PDT depth barrier due to excellent penetration of 6 MeV X-ray radiation through biological tissue. In addition, the conjugation of our NPs with folic acid moieties enables specific targeting of HCT116 cancer cells that overexpress the folate receptors. We carried out physiochemical characterization of PLGA NPs, such as size distribution, zeta potential, morphology and in vitro release of VP. Cellular uptake activity and cell-killing effect of these NPs were also evaluated. Results and discussion: Our results indicate that our nanoconstructs triggered by 6 MeV X-ray radiation yield enhanced PDT efficacy compared with the radiation alone. We attributed the X-ray-induced singlet oxygen generation from the PS, VP, to photoexcitation by Cherenkov radiation and/or reactive oxygen species generation facilitated by energetic secondary electrons produced in the tissue. Conclusion: The cytotoxic effect caused by VP offers the possibility of enhancing the radiation therapy commonly prescribed for the treatment of cancer by simultaneous PDT. Keywords: PLGA nanoparticles, verteporfin, singlet oxygen generation, photodynamic therapy, X-ray PDT, folic acid targeting
format	article
author	Clement S Chen W Deng W Goldys EM
author_facet	Clement S Chen W Deng W Goldys EM
author_sort	Clement S
title	X-ray radiation-induced and targeted photodynamic therapy with folic acid-conjugated biodegradable nanoconstructs
title_short	X-ray radiation-induced and targeted photodynamic therapy with folic acid-conjugated biodegradable nanoconstructs
title_full	X-ray radiation-induced and targeted photodynamic therapy with folic acid-conjugated biodegradable nanoconstructs
title_fullStr	X-ray radiation-induced and targeted photodynamic therapy with folic acid-conjugated biodegradable nanoconstructs
title_full_unstemmed	X-ray radiation-induced and targeted photodynamic therapy with folic acid-conjugated biodegradable nanoconstructs
title_sort	x-ray radiation-induced and targeted photodynamic therapy with folic acid-conjugated biodegradable nanoconstructs
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/7e8c001399a14713b41bd5ca99ed6a62
work_keys_str_mv	AT clements xrayradiationinducedandtargetedphotodynamictherapywithfolicacidconjugatedbiodegradablenanoconstructs AT chenw xrayradiationinducedandtargetedphotodynamictherapywithfolicacidconjugatedbiodegradablenanoconstructs AT dengw xrayradiationinducedandtargetedphotodynamictherapywithfolicacidconjugatedbiodegradablenanoconstructs AT goldysem xrayradiationinducedandtargetedphotodynamictherapywithfolicacidconjugatedbiodegradablenanoconstructs
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X-ray radiation-induced and targeted photodynamic therapy with folic acid-conjugated biodegradable nanoconstructs

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